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The information presented here is not intended to diagnose, treat, cure or prevent any disease. Always seek the advice of your own physician or other qualified health care professional. Read full Disclaimer.
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Filling the Gap
Dermal fillers are an important tool in the armamentarium of an aesthetic dermatologist in the management of ageing skin these days and its popularity is on the rise. But among dermal fillers the safe materials are short lasting while long lasting materials are not really safe. Certain materials that claim to be safe and long lasting by fibroblast activation do not have appropriate physico-mechanical properties. They are ‘bony hard’ and rarely even deposits bone! An ideal filler material should be biodegradable, non-cytotoxic, enhance fibroblast adherence and proliferation. It should also have ideal physico-mechanical properties. Scientists from University of Akron, Ohio doing research on biopolymers have stumbled upon such a material. [1] It is still early days and the research team has not even declared it as a probable dermal filler material.
‘Pseudo’ poly (aminoacids) such as L-Tyrosine polyurethanes (LTUs) have been synthesized by the structural modification of poly (aminoacids) by incorporation of non-peptide bonds into the polymer’s backbone. These bioplolymers have superior mechanical properties (particularly their excellent elasticity) without cytotoxic degradation products. They augment fibroblastic adhesion and proliferation that is even tunable to certain extend by subtle changes in the polymer structure.
I dare go to the extent of predicting it as a next generation hair loss treatment because of its ideal rheological properties as a scaffold for blood-vessel generation as I hypothesised before.
GlaxoSmithKline has a unique topical steroid molecule called GW870086 in the pipeline that could change the way we treat inflammatory skin disorders. [2] A modification of the 17α position of the steroid nucleus resulted in a molecule that retained the effect on anti-inflammatory targets while having minimal impact on the expression of other known target genes responsible for the side effects. The properties of GW870086 were compared to fluticasone propionate (FP) using a range of model systems, including extensive gene expression profiling. Murine models of irritant-induced contact dermatitis showed promising results. If the same efficacy and safety profiles can be demonstrated on humans as well, it may fulfill our long quest for a safe topical steroid.
Special thanks to Dr Yun of University of Akron and Dr Uings of GSK and their respective teams for the details.
References:
1. Shah, Parth N, and Yang H Yun. "Cellular interactions with biodegradable polyurethanes formulated from L-tyrosine." Journal of Biomaterials Applications (2011).
2. Uings, IJ et al. "Discovery of GW870086: A potent anti‐inflammatory steroid with a unique pharmacological profile." British journal of pharmacology (2013).
Labels: Dermal Filler, Drugs, Fibroblast, Tyrosine
The Angry Back
Have you had patients with an ‘Angry Back’ showing positive reaction to several patch test allergens? Or do you have stasis dermatitis patients sensitive to several allergens? [1]
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| English: 2+ patch test reaction (Photo credit: Wikipedia) |
"Polysensitisation" (PS) is usually defined as contact sensitisation to 3 or more unrelated haptens of the baseline patch test series. It is debatable whether the PS phenotype represents a distinct genotype or a natural staggered progression from a uni to oligo to polysensitisation process. Statistical modelling for identifying risk factors for this ill defined PS phenomena to 3 or more ‘unrelated’ haptens is difficult. Bivariate analysis and logical regression models were unsatisfactory.
This recent article [2] in BJD explores the concept of Polysensitisation (PS) in contact dermatitis using an interesting and novel methodology using a colossal central European dataset of about 140,000 patch test results. They have used a negative binomial hurdle regression method for count data to independently estimate risk to be sensitised at all and the risk of having several contact allergies, i.e., to be polysensitised.
The axillae and the feet were found to be strong PS risk factors along with increasing age and female sex. In comparison, atopic eczema and occupational dermatitis were less important risk factors.
The size of their dataset and the novel methodology makes this the most authoritative study of this unique phenomenon.
Special thanks to Dr. Wolfgang Uter and the rest of the team for the details.
References:
1. OD - CoD - http://gulfdoctor.net/acd/ (Object Database for Contact Dermatitis)
2. Schwitulla, J et al. "Risk factors of polysensitisation to contact allergens." British Journal of Dermatology (2013). http://onlinelibrary.wiley.com/doi/10.1111/bjd.12423/abstract
Labels: Contact dermatitis, Patch test (medicine), Regression analysis
#MapMyGenome
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| Animation of the structure of a section of DNA. The bases lie horizontally between the two spiraling strands. (Photo credit: Wikipedia) |
How many times your psoriasis or vitiligo patients wanted to know the risk of their kids developing the disease? I am sure you have also noticed the horror on the face of the adolescent staring at his father’s shiny bald scalp or the young girl seeing the undeniable stain of melasma spreading on her mother’s face. All these conditions are neither life threatening nor debilitating, but the psychological morbidity is enormous. We have also prayed in silence before starting Imuran for the CAD patients in distress hoping that they were not unlucky enough to be in the 0.3% with faulty TPMT.
We have been trying to reduce their anxiety by giving the general risk of inheritance till now, but we will soon be empowered to give the specific risk of the individual based on his/her genetic makeup. The technology has been there for sometime to screen specific areas of an individual’s genome (DNA) to identify SNPs (snips) that could make your risk prediction more accurate, but it was beyond the reach of most people especially in countries like India.
Ms. Anuradha Acharya, the young biotech entrepreneur who leveraged Indian bioinformatics expertise with Ocimum bio solutions is doing it again with mapmygenome, a ‘personal genomics’ initiative to take this technology to the masses. It is still in early stages and it covers only Lupus, Melanoma and Psoriasis from a dermatologist’s list of potential interest, but more specific test series will be available soon. All you need to provide is a saliva sample with a swab.
The potential benefits go beyond risk prediction and prognostic applications. Once enough data is available, the depersonalised population statistics would be an invaluable research tool for Indian population geneticists. More information about this, including how to order the test is available from the website http://mapmygenome.in/ .
Special thanks to Ms. Acharya for finding time to brief me on this.
Labels: DNA, melanoma, Personal genomics, Single-nucleotide polymorphism
The stem cell Line
What are the challenges in stem cell therapy? No, I am not talking about the Apple stem cell cream your beauty therapist gave you that is supposed to wipe away the wrinkles on your face like a magic wand and you actually believed, for the umpteenth time, that maybe you are going to become young again. Here I am talking about your own ‘real’ stem cells!
You need to identify a source, isolate and selectively amplify the correct type, ensure differentiation into the correct terminal cell type and find a way to actually put them in the correct place. Not something as simple as eating an apple. So if you want to treat a non-healing ulcer with keratinocyte stem cells, how do you get them without making another breach in the epidermis?
Dr Nair and Dr Krishnan from Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, India found that 4% of peripheral blood mononuclear cell in the blood are keratinocyte progenitor cells (KPCs) with the specific KPC marker p63 that can be harvested easily. [1] They have designed a biomimetic niche that can amplify it up to 70%. Within 12 days of culture, the cells coexpressed p63, CK5, and CK14 ensuring a keratinocyte lineage. Differentiation progressed during subculture and expressed involucrin and filaggrin indicating terminal keratinocyte differentiation. Since desmosomal connections are absent these cells can be easily transferred to a fibrin/fibroblast sheet ideal for transplantation as a skin substitute.
The two other stem cells of dermatological importance are melanocyte and hair progenitors. The former is difficult to amplify while the latter is difficult to find. Hope with the breathtaking developments in stem cell research, we would find a way soon!
References:
1. Nair, RP. "Identification of p63+ keratinocyte progenitor cells in circulation and ..." 2013. < http://stemcellres.com/content/4/2/38>
Labels: Biotechnology, Hair, Melanocyte, stem cell
Opposite Poles
Have you ever had this dream? Patients sitting outside your office waiting for their monthly infusion of stem cells. The polygel electrode of your next-gen skin rejuvenator not only replenishes the skin stem cell reserve but also removes any degraded cell fragments. Well, sit tight. This ‘fountain of youth’ technology may be just around the corner!
Like tiny crawling compass needles, whole living cells and cell fragments orient and move in response to electric fields - but in opposite directions, scientists at the University of California, Davis, have found. [1] This technology could open up new ways to safely and effectively deliver stem cells and remove unwanted cell fragments.
Another study explores the usefulness of human in vitro models to understand the mechanisms of skin ageing. [2] They have successfully used UVA-irradiated dermal fibroblasts to investigate the anti-ageing effects of sargachromanol E isolated from a marine brown alga, Sargassum horneri.
References:
1. "Opposites attract: How cells and cell fragments move in electric fields." 2013. 7 May. 2013 < http://www.news.ucdavis.edu/search/news_detail.lasso?id=10540>
2. Kim, JA. "The chromene sargachromanol E inhibits ultraviolet A-induced ..." 2012. < http://www.ncbi.nlm.nih.gov/pubmed/23278330>
Labels: Anti-ageing, Fibroblast growth factor, stem cell, UV light
Hurting the fly
Have you been hurting your patients with lasers, derma rollers or mesotherapy to initiate a wound healing response that promotes collagen synthesis and anti-ageing? I have blogged about a new laser technology from Philips before. But soon you may be able to initiate the same response without causing any injury at all. No, I am not going back to peptides again.
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| A syncytium forms after wounding the Drosophila epithelium. (Photo credit: Wikipedia) |
Many of the breakthroughs in clinical medicine is inspired by basic research and cosmetic dermatology is no exception. Scientists from University of California have recently published their findings on wound repair in Drosophila or the ubiquitous fruit fly and found some new genes involved in the process. [1] More than the list of new genes they have unearthed, the novel methodology they have employed in their study is of relevance in cosmetic dermatology in spite of the huge difference between the fruit fly and human fly.
The researchers have found that the serine protease trypsin is sufficient to induce a striking global epidermal wound response without inflicting cell death or compromising the integrity of the epithelial barrier and this could be applicable to humans as well. This "woundless wound healing cascade" could have many applications in cosmetic dermatology. Another curious finding was the absence of wound site melanization in trypsin wounded embryos while melanisation was common after puncture wounds. Though the primary focus of the paper was not melanisation and the authors have not discussed it much, this could well realise our dream of ‘controlled injury without the risk of post inflammatory hyperpigmentation’!
References:
1. Patterson, Rachel A et al. "Serine Proteolytic Pathway Activation Reveals an Expanded Ensemble of Wound Response Genes in Drosophila." PLOS ONE 8.4 (2013): e61773.
Labels: Anti-ageing, Hyperpigmentation, Wound healing
Chicken or the egg in Acne?
This article [1] reiterates the role of antimicrobial peptides (AMP), the body’s innate antimicrobial system in the pathogenesis and management of acne. Yes, there is a paradox here! AMP because of its anti-p.acnes action may improve acne while its proinflammatory properties may worsen it. It is not known whether p.acnes indirectly causes inflammatory acne by promoting AMP production. The authors examines several endogenous AMPs and gets unduly enticed in this Chicken-Egg paradox making too many speculations. However the bottom line seems to be simple and straightforward: Structurally modified AMPs and AMPs from other species with less proinflammatory properties may be useful in acne. Full article is available from the cited URL. [1]
Here is a head-to-head comparison of three questionnaires to screen for psoriatic arthritis. [2] All three questionnaires (PEST, Toronto Psoriatic Arthritis Screen (ToPAS) and PASE) were found to be effective for the purpose.
References:
1. Harder J, Tsuruta D, Murakami M, Kurokawa I. What is the role of antimicrobial peptides (AMP) in acne vulgaris? Exp Dermatol. 2013 Apr;p. n/a. Available from: http://dx.doi.org/10.1111/exd.12159.
2. Coates LC, Aslam T, Al Balushi F, Burden AD, Burden-The E, Caperon AR, et al. Comparison of three screening tools to detect psoriatic arthritis in patients with psoriasis (CONTEST study). The British journal of dermatology. 2013 Apr;168(4):802-807. Available from: http://dx.doi.org/10.1111/bjd.12190.
Labels: Acne vulgaris, AMP, Inflammation, Psoriasis, Psoriatic arthritis
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